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Antithrombin III in oral contraceptive users and during normotensive pregnancy.

Plasma antithrombin III (AT III) was determined in four groups of subjects, by employing an automated chromogenic technique. In 25 women, discontinuing oral contraceptives led to a 9% elevation of AT III, while in 13 women AT III levels fell by 9% after starting with the pill. In 77 normotensive pregnant patients AT III levels were normal during the third trimester and did not differ from control values 6-8 weeks after delivery. Women taking the pill at that time did not have lower AT III levels than those who did not. Furthermore, AT III levels in 414 oral contraceptive users were the same as in 572 controls, when random samples were taken during pill cycle and menstrual cycle. It is concluded that although synthetic estrogens do cause a decrease in AT III levels, this decrease is probably the result of estrogen-induced hemodilution, which may also occur during the normal menstrual cycle. If low dose pills are thrombogenic, mass screening for AT III deficiency will not identify those at risk, with the exception of the rare cases of hereditary AT III deficiency.

Adult↗

Structural anomalies of the cervix and vagina in women enrolled in the Diethylstilbestrol Adenosis (DESAD) Project.

Among women exposed in utero to diethylstilbestrol (DES) and enrolled in the Diethylstilbestrol Adenosis (DESAD) Project, structural anomalies of the cervix or vagina were found in 25% of the 1,655 subjects identified by review of prenatal records, 43% of the 800 who themselves requested entry into the project, and 49% of the 1,089 referred by physicians but in only 2% of the 963 control subjects. Among the 367 cases found by record review to have complete information on the DES exposure, multivariate analysis indicated close association of the anomalies with the gestational week of first exposure and the total dose. Also, the prevalence rate of the anomalies was lower among subjects who had been pregnant and higher among those with later age at menarche.

Abnormalities, Drug-Induced↗

Serum levels of 3-keto-desogestrel after oral administration of desogestrel and 3-keto-desogestrel.

In a cross-over study with orally administered desogestrel (0.150 mg) plus ethinyloestradiol (0.030 mg) and 3-keto-desogestrel (0.150 mg) plus ethinyloestradiol (0.030 mg) in ten women under steady-state conditions, the serum levels of 3-keto-desogestrel were monitored by radioimmunoassay. No statistically significant differences between treatment groups were found with respect to the areas under the curve of the serum levels versus time (AUC), peak heights and peak times. The individual AUCs for 3-keto-desogestrel after dosing with desogestrel (plus EE) or 3-keto-desogestrel (plus EE) show a similar degree of variation. The biotransformation of desogestrel into 3-keto-desogestrel is rapid and appears not to be limited by the metabolic capacity of the normal liver.

Administration, Oral↗

Plasma levels of cortisol and corticosteroid binding globulin during use of Norplant-2 implants.

Plasma levels of cortisol and corticosteroid binding globulin (CBG) were studied during one year in eleven healthy women using NORPLANT-2 implants. NORPLANT-2 implants release approximately 50 ug of levonorgestrel/day. A significant diurnal variation of cortisol levels was found during the study. No significant change in cortisol levels compared to pretreatment levels was found. Levels of CBG showed no diurnal variation, but decreased significantly during use of the implants. This was most probably due to a direct effect of the levonorgestrel, as the levels of estradiol did not change compared to pretreatment levels, except for the values after 6 months that were significantly lower than pretreatment levels. A "free cortisol index" calculated as: level of cortisol/level of CBG, was unchanged during treatment compared to pretreatment levels. It is concluded that although CBG levels were reduced, no significant change in cortisol patterns was seen during use of the implants.

Adult↗

Vaginal bleeding patterns among women using one natural and eight hormonal methods of contraception.

Menstrual diary records were obtained from a total of 5257 women using nine different methods of contraception, one natural and eight hormonal. This paper presents a comparative analysis of their vaginal bleeding patterns. The analytic procedures follow the recommendations of a recent WHO workshop on bleeding pattern analysis, which involve dividing each subject's diary into successive 90-day reference periods, calculating ten indices for each period, and classifying women according to whether they have "clinically important" bleeding disturbances. In general, the findings of this analysis confirm those of previous studies. Women using the natural method, who were deliberately selected for the regularity of their menstrual cycles, averaged three bleeding/spotting episodes of length 5 days in each 90-day period, with very little variability within or between women. Subjects given a combined oral contraceptive had more regular patterns than any other treated group, with short (4-day) episodes and 23-24 day bleeding-free intervals. Progestogen-only pill users had more frequent, longer episodes and shorter, less predictable intervals than combined pill users. Contrary to widely-held beliefs, the progestogen-only pills produced fewer spotting days than the combined pills, and almost no spotting episodes at all. Nearly half of vaginal ring users experienced some menstrual disturbance in each period; their most common problems were irregular, infrequent or prolonged bleeding. Women using the long-acting injectable, depot medroxyprogesterone acetate, had totally unpredictable patterns, with infrequent but prolonged bleeding/spotting episodes. The incidence of amenorrhea rose from just under 10% in their first injection interval to over 40% in their fourth. The methods of analysis recommended by WHO in 1985 still require substantial refinement. Nevertheless, they are more sensitive than those used previously for WHO trials and produce an easily understood, clinically meaningful characterization of bleeding patterns.

Administration, Intravaginal↗

Induction of ovulation in patients with normoprolactinemic amenorrhea by combined therapy with bromocriptine and clomiphene.

Bromocriptine is known to be effective in the treatment of women with hyperprolactinemic anovulation or amenorrhea-galactorrhea. A new schedule of combined treatment with bromocriptine and clomiphene citrate was applied to 23 patients with normoprolactinemic amenorrhea who failed to respond to clomiphene alone. Ovulation was restored by treatment in 14 of these patients (60.9%), resulting in pregnancy in 3 women. Treatment resulted in immediate suppression of serum prolactin levels and a gradual increase in serum luteinizing hormone levels and estradiol levels followed by a luteinizing hormone surge. The present results indicate that bromocriptine/clomiphene combination therapy is effective in the treatment of amenorrheic patients with normoprolactinemia who do not respond to clomiphene alone, and suggest that bromocriptine restores the responsiveness of the hypothalamic-pituitary-ovarian system to clomiphene.

Adult↗

Oral contraceptive agents do not affect serum prolactin in normal women.

A total of 230 healthy women attending family planning clinics took part in a cross-sectional study, comparing contraceptive histories and serum prolactin levels. It was found that the distribution histogram of serum prolactin was markedly skewed to the right in all main groups, but that the distribution profile was not affected by use of oestrogen-containing contraceptives. Neither the dose of oestrogens nor duration of their use affected prolactin levels. We have thus found that currently available combined oral contraceptive agents have no effect on serum prolactin. Analysis of the skewed raw data yields a 'normal' range of 110-700 mU/l, higher than that usually accepted.

Adolescent↗

Spermatogenesis in men treated with injections of medroxyprogesterone acetate combined with testosterone enanthate.

The effects of a combination of medroxyprogesterone acetate and testosterone enanthate, on the exocrine and endocrine testicular function were examined in adult men. The treatment was carried out with 2 different regimens and lasted for 8 months. Group I received an initial injection of 1000 mg medroxyprogesterone acetate and 500 mg testosterone enanthate followed by monthly maintenance dose of 150 mg medroxyprogesterone acetate and 500 mg testosterone enanthate. In group II, after an initial high dose of 1000 mg medroxyprogesterone acetate and 250 mg testosterone enanthate treatment was given as biweekly injections of 75 mg medroxyprogesterone acetate and 250 mg testosterone enanthate. Complete spermatogenic arrest of variable duration was achieved in all 9 subjects enrolled. Restoration of spermatogenesis occurred in both groups, in a few cases during the treatment, and there was a delay of full recovery of sperm counts up to 5 months after cessation of therapy. None of the subjects enrolled in this study complained of decrease in libido or change in sexual behaviour. Clinical evaluation and measurements of various urine and serum components revealed no significant changes during the treatment period. The dosage and the different administration schedule of the hormone combination described here was inadequate to maintain azoospermia in all subjects during treatment.

Adult↗

The influence of oral contraceptives on activated factor X inhibitor (XaI)-activity: a prospective study.

A prospective study of activated factor X inhibitor (XaI)-activity has been performed in women randomly allocated to contraceptive pills containing 30 micrograms + 150 micrograms (63 women) or 50 micrograms + 250 micrograms (44 women) ethinyl oestradiol and levonorgestrel, and a reference group of 35 women using other contraceptive methods. The XaI-activity was measured six times during 1 year of observation. There was a significant reduction of XaI-activity after 1 month of oestrogen consumption but there was no significant difference between 30 and 50 micrograms users. The maximal reduction during the observation period was 12% in both groups. There was positive correlation between the pretreatment value and the maximal reduction in the same patient, but the activity did not fall below the normal range (75-125% of normal human plasma).

Adult↗

Prednisolone disposition and protein binding in oral contraceptive users.

Combined estrogen-progestogen oral contraceptives (OC) have been shown to alter the metabolism of certain drugs, including corticosteroids, as well as affect circulating protein concentrations. To assess these effects with regard to prednisolone, the pharmacokinetics and protein binding of this steroid were evaluated in eight female OC users and compared with results from eight male and five female non-OC users. All volunteers received 40 mg prednisolone, iv, and steroid concentrations were measured by high pressure liquid chromatography. Plasma clearance of total prednisolone in females on OC was 96 +/- 9 (SD) ml/min X 1.73 m2, significantly (P less than 0.001) lower than those in both male and female controls (205 +/- 46 and 187 +/- 22 ml/min X 1.73 m2). The prednisolone half-life and mean residence time were longer, while the steady state volume of distribution was smaller for OC users. Unbound prednisolone was measured by equilibrium dialysis, and pharmacokinetic and protein binding parameters were calculated from free prednisolone concentrations. A significantly higher (2-fold) concentration of transcortin was found in OC users. Evaluation of free prednisolone parameters showed a significantly lower clearance and decreased volume of distribution, without alteration of the mean residence time for the OC users. Dual OC effects on binding and elimination of prednisolone occur with the net result of a 2-fold increase in the area under the free concentration-time curve, indicative of a marked reduction in the biotransformation rate of the steroid.

Adult↗

[Post-pill amenorrhea and anovulation (author's transl)].

The numerous pregnancies that occur as early as the first cycle after the discontinuation of an oral contraceptive prove that in general ovulation reappears immediately and that after a period of "rest" more or less prolonged the ovaries reasume their normal function very rapidly. However, in less than 1% of the cases the discontinuation of oral contrecption is followed by anovulation or even amenorrhea. The authors try to find an explanation to this over supression syndrome and review the different treatments that have been proposed in the bibliography, but keeping in mind that within a year 14% of the anovulations and 5% of the amenorrbeas will have disappeared spontaneously.

Age Factors↗

Clinical and pathological comparison of young adult women with hepatocellular carcinoma with and without exposure to oral contraceptives.

We compared the clinical characteristics and histological classifications of young adult women with hepatocellular carcinoma with and without exposure to increased amounts of sex steroids in order to investigate the possibility that sex steroids changed the behavior of the tumor. Fifteen women were found to have a history of exposure to increased levels of sex steroids while 14 did not. One of the women in the exposed group had elements of adenoma next to her carcinoma, allowing speculation as to whether the malignancy arose from a previous adenoma. Statistically significant differences between the two groups were that the exposed group had a higher number of gravida (2.2 compared to 0.9, p = 0.013) and suffered tumor rupture with hemoperitoneum more frequently (4/15 compared to 0/4, p = 0.037). Trends worth noting were that the exposed group tended to survive longer, complain of pain and weight loss less frequently, and have lower alpha-fetoprotein levels. These findings indicate that exposure to sex steroids may change the clinical behavior of hepatocellular carcinoma, producing among other things a hypervascularity and tendency for hemoperitoneum.

Adult↗

Depo-Provera in the treatment of recurrent vulvovaginal candidiasis.

The long-acting injectable progestogen Depo-Provera appears to substantially reduce women's susceptibility to recurrent vulvovaginal candidiasis. Pregnancy and exogenous estrogen appear to counteract this effect of the drug. Evidence was derived from 15 patients studied for up to six years.

Adult↗